DESCRIPTION (Taken from the applicant's abstract) The prevalence of obesity in the U.S. ranges from 25% overall to greater than 50% in some minority groups. Obesity may constitute the most common health problem in America, with associated morbidity and mortality rates equal to that of cancer. However, therapeutic options remain largely ineffectual. Thus, research into the pathophysiology and treatment of obesity assumes great significance to national health. Recent studies have demonstrated the importance of the brain, and specifically hypothalamus, to the regulation of body weight. Several hypothalamic substances have been identified which dramatically alter appetite and metabolic rate. In the present study, we have chosen to investigate the role of one particularly interesting hypothalamic neuropeptide, melanin concentrating hormone (MCH). Toward this end, transgenic mouse strains overexpressing the MCH gene will be produced. These strains should provide information regarding the physiologic actions of MCH in body weight regulation. In addition, the transgenic mice may constitute useful models for examining the actions of potential anti-obesity treatments. As an alternative approach, the effects of MCH administration by direct intracerebral injection will be studied. Dr. Ludwig's main research area is the neuroendocrine control of appetite and metabolism. In particular, he is interested in understanding how abnormal structure and function of the hypothalamus may underlie body weight disorders. The project will be conducted in the Division of Endocrinology and Metabolism of Beth Israel Hospital, Boston, under the supervision of Dr. Jeffrey Flier (Division Chief). Obesity and diabetes comprise the predominant research focus of the Division. Specific projects involve studies of insulin signal transduction, brown adipose tissue function, and leptin. The research environment contains state-of-the-art molecular biology, animal research, and transgenic facilities.